Microcrystalline cellulose is a purified, partially depolymerized cellulose that is produced by treating a source of cellulose, preferably alpha cellulose in the form of pulp from fibrous plant materials, with a mineral acid, preferably hydrochloric acid. The acid selectively attacks the less ordered regions of the cellulose polymer chain thereby exposing and freeing the crystalline sites which form crystallite aggregates which constitute the microcrystalline cellulose. These are then separated from the reaction mixture, and washed to remove degraded by-products. The resulting wet mass, generally containing 40 to 60 percent moisture, is referred to in the art by several names, including hydrolyzed cellulose, level-off DP cellulose, microcrystalline cellulose, microcrystalline cellulose wetcake or simply wetcake.
When the wetcake is dried and freed of water, the resulting product, microcrystalline cellulose, is a white, odorless, tasteless, relatively free-flowing powder, insoluble in water, organic solvents, dilute alkalis and acids. For a fuller description of microcrystalline cellulose and its manufacture see U.S. Pat. No. 2,978,446. The patent describes its use as a pharmaceutical excipient, particularly as a binder, disintegrant, flow aid, and/or filler for preparation of compressed pharmaceutical tablets. Microcrystalline cellulose is manufactured by FMC Corporation and sold under the designation Avicel.RTM. PH cellulose in several grades having average particle sizes ranging from about 20 .mu.m to about 180 .mu.m.
In wet granulations using microcrystalline cellulose, for example Avicel.RTM. PH 101, at least one additional ingredient has been required to be used as a binder. Typical binders include corn starch paste, pregelatinized starch, ethyl cellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone. Although the corn starch must be dispersed in water to be used in wet granulations, the other binders are often dispersed in water prior to the granulation step to increase their effectiveness. The use of these binders therefore adds additional steps to the granulation process resulting from having to weigh out the individual binders and disperse them in water as needed. An additional consequence is to increase the inventory of excipients. Accordingly there is a need for a single dry, ready-to-use excipient for use in granular and/or tableted pharmaceutical preparations.
U.S. Pat. No. 5,366,742 discloses an aggregate of highly attrited, colloidal microcrystalline cellulose coprocessed with a sodium, calcium alginate complex and use of the resulting aggregate as a readily water dispersible suspending agent for food products such as salad dressings, frozen desserts, dry cocoa mixes and the like. The patent describes the alginate used as a high viscosity sodium alginate which is complexed with calcium to form the sodium, calcium alginate complex.
It has now been found that unattrited microcrystalline cellulose wetcake coprocessed with a low viscosity alginate is more effective as an excipient/binder than prior combinations of microcrystalline cellulose with the binders listed above. This effectiveness is observed in the excellent binding qualities in the granulations and the ease and speed with which they can be prepared. This increased binding effectiveness carries over into the tablets prepared by compressing the granulations, translates into reduced damage to tablets during compression, coating, packaging, and transporting the product to the ultimate user, provides tablets having unexpectedly low friability, and facilitates increased productivity in the manufacturing and handling operations.
These and other advantages and objects of the invention are provided by using as an excipient/binder for pharmaceutical granulations and tableting unattrited microcrystalline cellulose wetcake coprocessed with low viscosity sodium alginate as hereinafter described.